Everolimus-Facilitated Tacrolimus Minimization Preserves Renal Function in De Novo Renal Transplant Recipients.
Bibliographic record
Abstract
Introduction:Reducing CNI exposure in renal transplant recepients (RTxR) may have a positive impact on renal function (RF). The current study (NCT01025817) assessed the efficacy and safety of everolimus (EVR)+low-dose tacrolimus (LTac) vs mycophenolate mofetil (MMF)+standard-dose Tac (STac) regimen. Presented here are 12-month (M) RF results. Methods: In this 12M, multicenter (52 US & Canadian centers), randomized, open-label non-inferiority study, 613 de novo RTxR received EVR (starting at 0.75 mg bid)+LTac (n=309) or MMF (2 g/day)+STac (n=304). All patients (pts) received induction therapy (basiliximab if PRA<20%; or Rabbit anti-thymocyte globulin if PRA ≥20% or high risk) and steroids as per local practice. Primary endpoint was composite efficacy failure rate at 12M (tBPAR, graft loss, death, or lost to follow-up). RF (eGFR, mL/min/1.73 m2) was estimated using MDRD formula and proteinuria by urine protein/creatine ratio (UPC, mg/g). Results: The composite efficacy failure rate of EVR+LTac (24.6%; n=76) did not meet non-inferiority vs MMF+STac (20.4%; n=62) due to higher rate of acute rejection. Graft survival was significantly better with EVR+LTac vs MMF+STac (98.7% vs 96.1%; p<0.05). While the mean calculated eGFR was better in the EVR+LTac vs MMF+STac for the first 6M only and similar at 12M (63.14 vs 63.06), the on-treatment mean (66.21 vs 64.26) and median (65.93 vs 61.96) eGFR was consistently higher in the EVR+LTac arm for 12M. In addition, the mean eGFR at 12M was numerically higher with EVR+LTac vs MMF+STac in both subsets of pts with delayed graft function (DGF; 63.81 vs 58.48) and tBPAR (54.9 vs 52.96). Incidence of proteinuria was similar in EVR+LTac vs MMF+STac arm by 12M (UPC<500, 76.9% vs 75.4%; 500-<1000, 6.9% vs 5.2%; 1000-<2000 1% vs 2.6%; 2000-<3500 1.5% vs 0.4%; ≥3500 1% vs 0.4%). Mean UPC ratio 12M post-transplantation was similar with EVR+LTac vs MMF+STac (Figure).Figure: No Caption available.Conclusions: In de novo RTxR, EVR-based regimen with LTac preserved renal function without increasing proteinuria. This effect was most pronounced in DGF pts. eGFR was also similar between the treatment arms for pts with tBPAR. DISCLOSURES:Shihab, F.: Other, Novartis, Consultant and Speaker, Astellas, Consultant. Mulgaonkar, S.: Grant/Research Support, Novartis, Other, Novartis, Advisor. Peddi, V.: Grant/Research Support, Novartis, Astellas. Shaffer, D.: Grant/Research Support, Novartis. Patel, D.: Employee, Novartis Pharmaceutical Corporation. McCague, K.: Employee, Novartis Pharmaceutical Corporation. Vincenti, F.: Grant/Research Support, Novartis, Genzyme, Genentech, Astellas, Alexion, Pfizer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".